The goal of the proposed project is to design and build a large mosaic of CCD detectors to provide an improved film substitute for direct digital recording of data for biological electron rnicroscopy. Such a system will be immediately applicable and beneficial to cryo-electron microscopy (cryo-EM) of macromolecules and 3D electron tomography of macromolecular complexes, organelles, and cellular subsystems. For molecular microscopy (with cryo-EM), this system will enable the routine collection of up to l million images of large macromolecular complexes, facilitating and accelerating the determination of high-resolution structures of protein complexes, without the difficulty of growing large crystals of purified materials (as is otherwise the case with protein crystallography). The same new detector technology will also allow the collection of wide-field images for intermediate resolution 3D microscopy spanning multiple spatial scales, to enable determinations of the precise organization of supramolecular complexes throughout large functional domains of cells in tissues. Building on the recent success of lens-coupled CCD camera technology, our goal is to build a new detector containing a mosaic of 9 CCD detectors, each with its own lens that can cover an overlapping portion of a scintillator screen of 15 cm x l5 cm. This mosaic detector will have a functional resolution of 5600 x 5600 pixels. We will initially design and test a single "module" of this detector with one back-side illuminated 2K x 2K pixel (13.5 gm) CCD sensor and one prototype lens. This will be followed by the design and development of a 2 x 2 mosaic of detectors and lenses. This moderately complex mosaic camera will allow us to work out all design and development issues before making the 9 CCD mosaic in the 3rd year. A significant effort during all 3 years will be to map out all detector distortions and to develop software to seamlessly stitch together detector subimages.